Chromosome 3, Monosomy 3p

NORD gratefully acknowledges Shashikant Kulkarni, PhD, Director of CytoGenomics and Molecular Pathology, Director of Clinical & Molecular Cytogenetics, Department of Pathology, Washington University School of Medicine, for assistance in the preparation of this report.

Synonyms of Chromosome 3, Monosomy 3p

Chromosome 3, Deletion of Distal 3p

Chromosome 3, Distal 3p Monosomy

Monosomy 3p

General Discussion

Chromosome 3, Monosomy 3p is a rare chromosomal disorder in which the end (distal) portion of the short arm (p) of chromosome 3 is missing (deleted or monosomic). The range and severity of symptoms and findings may be variable. However, associated features often include growth delays before and after birth (prenatal and postnatal growth deficiency); severe to profound mental retardation; distinctive malformations of the skull and facial (craniofacial) region; eyebrows that grow together (synophrys); and/or excessive hair growth (hypertrichosis). Additional physical abnormalities may also be present. In many cases, Chromosome 3, Monosomy 3p appears to occur spontaneously (de novo) for unknown reasons.

Signs & Symptoms

As noted above, the symptoms and physical findings associated with Chromosome 3, Monosomy 3p may vary in range and severity from case to case. However, according to reports in the medical literature, many affected individuals have a low birthweight; marked growth delays after birth (postnatal growth retardation); severe to profound mental retardation; severe delays in the acquisition of skills requiring the coordination of mental and motor activities (psychomotor retardation); excessive hair growth (hypertrichosis); and/or distinctive malformations of the skull and facial (craniofacial) region.

Many affected infants have an abnormally small head (microcephaly) that may appear unusually short and broad (brachycephaly); a flat back region of the head (occiput); and/or an abnormally high, narrow, prominent forehead. Additional craniofacial abnormalities may include a triangular face; arched eyebrows that grow together (synophrys); a broad, flat nose; an unusually long vertical groove in the middle of the upper lip (philtrum); thin lips; and/or an abnormally small lower jaw (mandible). Affected individuals may also have a downwardly turned mouth; widely spaced eyes (ocular hypertelorism); vertical skin folds that cover the eyes’ inner corners (epicanthal folds); upwardly slanting eyelid folds (palpebral fissures); drooping of the upper eyelids (ptosis); and/or low-set, malformed ears.

Chromosome 3, Monosomy 3p is also commonly associated with more than the normal number of fingers and/or toes (polydactyly). In many cases, there may be additional fingers, particularly duplication of the “pinkies” or fifth fingers (postaxial polydactyly). In addition, in some instances, affected infants may have duplication of certain toes, particularly the fifth toes.

Reports indicate that some affected individuals may also have hearing loss and/or visual impairment. In addition, the disorder may be associated with additional physical features, such as abnormal forward (anterior) placement of the anus; undescended testes (cryptorchidism) in affected males; kidney (renal) defects: structural malformations of the heart (congenital heart defects); and/or other abnormalities.

Causes

Chromosome 3, Monosomy 3p is a rare chromosomal disorder in which there is deletion (monosomy) of the end (distal) portion of the short arm (p) of chromosome 3. Researchers indicate that symptoms and findings characteristic of the syndrome result from deletion of chromosomal material extending from band 25 on the short arm of chromosome 3 (breakpoint) to the end or “terminal” of 3p (3p25–>pter). Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as “p” and a long arm identified by the letter “q”. Chromosomes are further subdivided into bands that are numbered. Therefore, 3p25 refers to band 25 on the short arm of chromosome 3.

In most reported cases, Chromosome 3, Monosomy 3p has appeared to result from spontaneous (de novo) errors very early in embryonic development. In such instances, the parents of the affected child usually have normal chromosomes and a relatively low risk of having another child with the chromosomal abnormality.

All cases of Monosomy 3p except for one have been new chromosomal changes (de novo). In one case, the deletion was inherited from the mother who had the same deletion 3p. Potentially, monosomy 3p could result from a parental translocation or inversion.

Translocations occur when regions of certain chromosomes break off and are interchanged, resulting in shifting of genetic material and an altered set of chromosomes. If such chromosomal rearrangements are “balanced”, all of the chromosomal material is present in two copies but at different locations. Balanced translocations are usually harmless to the carrier. However, such chromosomal rearrangements may be associated with an increased risk of abnormal chromosomal development in the carrier’s offspring if inherited in an “unbalanced” state. An unbalanced translocation occurs when only one of the two chromosomes involved in the translocation is inherited from a carrier parent. The result is too much (duplication or trisomy) or too little (deletion or monosomy) chromosomal material. An inversion occurs when a chromosome breaks in two places within a single chromosome and the segment between the breaks rejoins the chromosome in the reverse order. Chromosomal analysis and genetic counseling are typically recommended for parents of an affected child to help confirm or exclude a chromosomal rearrangement in one of the parents.

Affected Populations

Chromosome 3, Monosomy 3p appears to affect males and females in relatively equal numbers. Since the disorder was originally reported in 1978 (Verjaal M), approximately 34 cases have been described in the medical literature.

Related Disorders

Additional chromosomal disorders may have features similar to those associated with Chromosome 3, Monosomy 3p. Chromosomal analysis is necessary to confirm the specific chromosomal abnormality present. (For further information on such disorders, choose the name of the specific chromosomal disorder in question or use “chromosome” as your search term in the Rare Disease Database.)

Diagnosis

In some cases, Chromosome 3, Monosomy 3p may be suggested before birth (prenatally) by specialized tests such as ultrasound, amniocentesis, and/or chorionic villus sampling (CVS). During fetal ultrasonography, reflected sound waves create an image of the developing fetus, potentially revealing certain findings that suggest a chromosomal disorder or other developmental abnormalities in the fetus. With amniocentesis, a sample of fluid that surrounds the developing fetus is removed and analyzed, while CVS involves the removal of tissue samples from a portion of the placenta. Chromosomal analysis performed on such fluid or tissue samples may reveal the presence of Monosomy 3p.

The disorder may also be diagnosed or confirmed after birth (postnatally) based upon a thorough clinical evaluation, detection of characteristic findings (e.g., growth delays, mental retardation, psychomotor retardation, craniofacial abnormalities, etc.), and chromosomal analysis. Specialized tests may also be conducted to help detect and/or characterize certain abnormalities that may be associated with the disorder.

Standard Therapies

Treatment

The treatment of Chromosome 3, Monosomy 3p is directed toward the specific symptoms that are apparent in each individual. Such treatment may require the coordinated efforts of a team of medical professionals, such as pediatricians; surgeons; neurologists; physicians who diagnose and treat heart abnormalities (cardiologists); hearing specialists; and/or other health care professionals. In some cases, physicians may recommend surgical repair of certain malformations associated with the disorder. The specific surgical procedures performed will depend upon the severity and location of the anatomical abnormalities, their associated symptoms, and other factors.

Early intervention may be important in ensuring that affected children reach their potential. Special services that may be beneficial include special education, physical therapy, and/or other medical, social, and/or vocational services. Genetic counseling will also be of benefit for families of affected children. Other treatment for this disorder is symptomatic and supportive.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:

Lukusa T, et al. A 3p deletion syndrome in a child with both del(3)(p25–>pter) and dup(17)(q23–>qter). Ann Genet. 1999;42:91-94.

Narahara K, et al. Loss of the 3p25.3 band is critical in the manifestation of del(3p) syndrome: karyotype-phenotype correlation in cases with deficiency of the distal portion of the short arm of chromosome 3. Am J Med Genet. 1990;35:269-73.

Higginbottom MC, et al. A second patient with partial deletion of the short arm of chromosome 3: karyotype 46,XY,del(3)(p25). J Med Genet. 1982;19:71-73.

Verjaal M, et al. A patient with a partial deletion of the short arm of chromosome 3. Am J Dis Child. 1978;132:43-45.

Years Published

1994, 2001, 2003, 2009

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